INCIDENCE, CHARACTERISTICS AND OUTCOME OF CNS INVOLVEMENT IN MANTLE CELL LYMPHOMA: A MULTICENTRE RETROSPECTIVE ANALYSIS FROM THE EUROPEAN MANTLE CELL LYMPHOMA NETWORK

Sborník

Background. CNS involvement in Mantle Cell Lymphoma (MCL) is an uncommon but devastating event. Limited data exist to define true incidence or clinical features. Aims. To describe the clinical characteristics and outcomes of patients with CNS involvement in Mantle Cell Lymphoma. Methods. The study design was a multicentre retrospective case series. 12 participating institutions provided 1) total number of patients in their MCL database, 2) number with CNS involvement and 3) detailed information including demographics, baseline characteristics, presentation, prior treatments, investigations, subsequent therapies and outcomes. Results. 1314 patients with MCL were included in this analysis. 53 patients with CNS involvement were identified between 1988 and 2011. The crude cumulative incidence of CNS involvement was 4.0%. Of those with CNS disease, 71% were male, median age 61 years (38 - 82). At diagnosis, 36 (68%) had classical MCL, 15(28%) blastoid histology. Among 26 patients with data, Ki67 value by immunohistochemistry was 60% or higher in 12 cases (46%). 91% of patients were stage IV, 52% had B symptoms at presentation, and the median white cell and lymphocyte counts were 17.5 x 109/L and 12.2 x109/L respectively. Among 24 patients with data, high MIPI score (6 or more) was seen in a striking 18(75%). 9 patients had CNS involvement at diagnosis. The commonest neurological symptoms were weakness (26%), altered mental state (25%), ocular/diplopia (21%) and headache (19%). Sensory disturbances were less common. 5% were asymptomatic. Lumbar puncture was performed in 46 patients, with 85% positive by cytology. Flow cytometry improved the yield to 91% in the 33 patients tested. Radiographic changes suggestive of CNS disease were seen in 36/44 (82%) cases performed, with leptomeningeal changes was present in 15/36 (42%) and cortical lesions in 11/36 (31%).Prior therapies were heterogeneous with a median of 2 prior treatments (0 - 6), the commonest regimen being (R)-CHOP like in 26 (49%) with 16 (30%) receiving CNS penetrating doses of methotrexate and cytarabine ie (R)-Hyper CVAD, R-maxiCHOP/high dose cytarabine). 18/45 (40%) patients with data received prior intrathecal prophylaxis. 36 (68%) of patients had concurrent systemic relapse at the time of their CNS relapse, with 15 (28%) having isolated CNS relapse. The median time to CNS relapse from diagnosis was 11.5 months, with 67% occurring within 2 years of diagnosis. 38 (72%) received chemotherapy alone as treatment for their CNS relapse, with 5 (9%) receiving combined modality incoroporating chemotherapy with radiotherapy. A further 5% were not offered active treatment. There was a predictably poor outlook once diagnosed (median OS 3.3 months) although 9 patients remain alive at the time of reporting (median survival from CNS diagnosis 3.9 months, range 0.9 to 63.2 months). Conclusions. This is the largest dataset describing CNS involvement in Mantle Cell Lymphoma with an estimated cumulative incidence of 4%. In particular, high MIPI score and high Ki67 were notable features. Most CNS relapse occurred within the first two years., suggesting that if high risk features can be targeted CNS prophylaxis as part of initial therapy may be effective in preventing CNS progression.

Haematologica, 2012; 97(s1):  457